# Preclinical trial for dysarthria treatment in Parkinson disease

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $653,455

## Abstract

PROJECT SUMMARY
Parkinson disease (PD) is devastating to communication, which is also impacted by concurrent cognitive and
affective impairments. The hallmark pathology, loss of dopamine, has guided therapy for decades; however,
dopamine-centered treatments do not improve vocal communication, cognition, or affect. In fact, prior to classic
dopamine loss, there is significant degeneration in the locus coeruleus, a norepinephrine-rich brainstem region
that is vital to communicative and cognitive behaviors. Here, we propose to study three different therapeutic
approaches that modulate norepinephrine (exercise, drugs, socialization) based on the rationale that
modulating noradrenergic brain systems will improve PD-related communication deficits, as well as cognition
and affect. We hypothesize that the benefit of these therapies will be improved communication, cognition, and
affect as well as neuroprotection (i.e. sparing of neurons, increased neurotrophins). However, as with any
treatment, there may be unwanted side effects such as anxiety, increased motor errors, or enhanced
neuroprogression (loss of neurons) due to neurotoxicity of drugs. For superior experimental control and to
study underlying neural mechanisms with increased scientific rigor, we will use a well-established translational
rat model. The Pink1-/- rat is based on a genetic form of early and progressive PD (PARK6) that is nearly
identical to idiopathic PD. We have shown communication, motor, cognitive, and affective deficits and neural
abnormalities that are analogous to humans, including early loss of norepinephrine in brain regions important
to communication. Aim 1 will analyze the benefits and side effects of intervention on communication, cognition,
and affect. Pink1-/- rats will be treated with either: (1) cardiovascular exercise, (2) targeted vocal exercise, (3)
methylphenidate, (4) propranolol, (5) social enrichment, or (6) control conditions at 10 months of age, which is
equivalent to human age at time of diagnosed and treatment initiation. Vocalization, attention, accuracy,
memory, anhedonia, and anxiety will be assayed, and effect sizes of each treatment will be calculated to
determine the impact of treatment on all outcomes. Aim 2 will quantify changes to the brain with these
interventions. Rats from Aim 1 will undergo in vivo microPET scanning to determine how interventions
modulate norepinephrine. Ex vivo, brain tissues will be analyzed for neurotransmitter content, cell numbers,
and changes to neurotrophins/receptors in regions associated with vocalization, cognition, and affect using
high pressure liquid chromatography and immunohistochemistry. We hypothesize that interventions will result
in either neuroprotection (e.g., increases in neurotrophic factors) or neurodegeneration (e.g., cell death/loss of
neurotransmitter). This work is innovative because it is the first controlled study to robustly assess behavioral
responses to noradrenergically-based interventions and ...

## Key facts

- **NIH application ID:** 10290887
- **Project number:** 5R01DC018584-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Michelle Renee Ciucci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $653,455
- **Award type:** 5
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10290887

## Citation

> US National Institutes of Health, RePORTER application 10290887, Preclinical trial for dysarthria treatment in Parkinson disease (5R01DC018584-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10290887. Licensed CC0.

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